Potential anticancer properties and mechanisms of thymoquinone in colorectal cancer.

Colorectal neoplasms are one of the deadliest diseases among all cancers worldwide. Thymoquinone (TQ) is a natural compound of Nigella sativa that has been used in traditional medicine against a variety of acute/chronic diseases such as asthma, bronchitis, rheumatism, headache, back pain, anorexia, amenorrhea, paralysis, inflammation, mental disability, eczema, obesity, infections, depression, dysentery, hypertension, gastrointestinal, cardiovascular, hepatic, and renal disorders. This review aims to present a detailed report on the studies conducted on the anti-cancer properties of TQ against colorectal cancer, both in vitro and in vivo. TQ stands as a promising natural therapeutic agent that can enhance the efficacy of existing cancer treatments while minimizing the associated adverse effects. The combination of TQ with other anti-neoplastic agents promoted the efficacy of existing cancer treatments. Further research is needed to acquire a more comprehensive understanding of its exact molecular targets and pathways and maximize its clinical usefulness. These investigations may potentially aid in the development of novel techniques to combat drug resistance and surmount the obstacles presented by chemotherapy and radiotherapy.

Vitamin D in respiratory viral infections: a key immune modulator?

Respiratory viral infections are common respiratory diseases. Influenza viruses, RSV and SARS-COV2 have the potential to cause severe respiratory infections. Numerous studies have shown that unregulated immune response to these viruses can cause excessive inflammation and tissue damage. Therefore, regulating the antiviral immune response in the respiratory tract is of importance. In this regard, recent years studies have emphasized the importance of vitamin D in respiratory viral infections. Although, the most well-known role of vitamin D is to regulate the metabolism of phosphorus and calcium, it has been shown that this vitamin has other important functions. One of these functions is immune regulation. Vitamin D can regulate the antiviral immune response in the respiratory tract in order to provide an effective defense against respiratory viral infections and prevention from excessive inflammatory response and tissue damage. In addition, this vitamin has preventive effects against respiratory viral infections. Some studies during the COVID-19 pandemic have shown that vitamin D deficiency may be associated with a higher risk of mortality and sever disease in patients with COVID-19. Since, more attention has recently been focused on vitamin D. In this article, after a brief overview of the antiviral immune response in the respiratory system, we will review the role of vitamin D in regulating the antiviral immune response comprehensively. Then we will discuss the importance of this vitamin in influenza, RSV, and COVID-19.

Melatonin: a pleiotropic hormone as a novel potent therapeutic candidate in arsenic toxicity.

BACKGROUND: Arsenic is a natural element which exists in the environment in inorganic and organic forms. In humans, the main reason for the toxicity of arsenic is its uptake via water sources. As polluted water and the problems associated with it can be found in many countries. Therefore, considering all these positive effects of melatonin, this review is aimed at melatonin supplementation therapy on arsenic toxicity which seems to be a suitable therapeutic agent to eliminate the adverse effects of arsenic. METHODS AND RESULTS: It is seen in previous studies that chronic exposure to arsenic could cause serious dys functions of organs and induce different degrees of toxicities that is one of the first hazardous materials in the classification of substances by the United States Environmental Protection Agency so leads to costly cleanup operations burdening the economy. Arsenic harmfulness degree depends on the bioavailability, chemical form, valence state, detoxification, and metabolism of human body. The oxidative stress has a major role in arsenic-induced toxicity; on the other hand, it was discovered that melatonin is a powerful scavenger for free radical and it's an extensive-spectrum antioxidant. CONCLUSION: Due to its highly lipophilic and small size properties, melatonin accesses all intracellular organs by easily passing via the cell membrane and prevents protein, DNA damage, and lipid peroxidation. In particular, melatonin, by protecting and reducing oxidative stress in mitochondria, can normalize homeostasis and mitochondrial function and ultimately prevent apoptosis and cell death.

Stabilization of telomere by the antioxidant property of polyphenols: Anti-aging potential.

Aging is a form of a gradual loss of physiological integrity that results in impaired cellular function and ultimately increased vulnerability to disease and death. This process is a significant risk factor for critical age-related disorders such as cancer, diabetes, cardiovascular disease, and neurological conditions. Several mechanisms contribute to aging, most notably progressive telomeres shortening, which can be counteracted by telomerase enzyme activity and increasing in this enzyme activity associated with partly delaying the onset of aging. Individual behaviors and environmental factors such as nutrition affect the life-span by impact the telomerase activity rate. Healthy eating habits, including antioxidant intakes, such as polyphenols, can have a positive effect on telomere length by this mechanism. In this review, after studying the underlying mechanisms of aging and understanding the relationships between telomeres, telomerase, and aging, it has been attempted to explain the effect of polyphenols on reversing the oxidative stress and aging process.

Quercetin attenuated oxidative DNA damage through NRF2 signaling pathway in rats with DMH induced colon carcinogenesis.

Accumulating recent studies have demonstrated the preventive and therapeutic effects of polyphonic compounds such as quercetin in colorectal cancer. Therefore, we aimed to evaluate the underlying mechanisms for positive effects of quercetin in rats with 1,2-dimethylhydrazine (DMH)- induced colorectal cancer. For this purpose, male Wistar rats were classified as 6 groups, including group 1 without any intervention, group 2 as quercetin received rats (50 mg/kg), groups 3 as DMH received rats (20 mg/kg) group 4-6 DMH and quercetin received rats. DNA damage, DNA repair, the expression levels and activities of enzymic antioxidants, non-enzymic antioxidants, and NRF2/Keap1 signaling were evaluated in colon tissues of all groups. Our results showed significant suppression of DNA damage and induction of DNA repair in DMH + Quercetin groups, particularly in entire-period in comparison to other groups (p < .05). The expression levels and activities of enzymic and non-enzymic antioxidants were increased in DMH + Quercetin groups (p < .05). Lipid and protein peroxidation were significantly suppressed in DMH + Quercetin groups (p < .05). In addition, quercetin also modulated NRF2/Keap1 signaling and its targets, detoxifying enzymes in DMH + Quercetin groups. Our finding demonstrated that quercetin supplementation effectively reversed DMH-mediated oxidative stress and DNA damage through targeting NRF2/Keap1 signaling pathway.

Therapeutic potential of polyphenols in cardiovascular diseases: Regulation of mTOR signaling pathway.

Cardiovascular diseases comprise of non-communicable disorders that involve the heart and/or blood vessels and have become the leading cause of death worldwide with increased prevalence by age. mTOR is a serine/threonine-specific protein kinase which plays a central role in many physiological processes including cardiovascular diseases, and also integrates various proliferative signals, nutrient and energy abundance and stressful situations. mTOR also acts as central regulator during chronic stress, mitochondrial dysfunction and deregulated autophagy which are associated with senescence. Under oxidative stress, mTOR has been reported to exert protective effects regulating apoptosis and autophagy processes and favoring tissue repair. On the other hand, inhibition of mTOR has been suggested to have beneficial effects against atherosclerosis, cardiac hypertrophy and heart failure, and also in extending the lifespan. In this aspect, the use of drugs or natural compounds, which can target mTOR is an interesting approach in order to reduce the number of deaths caused by cardiovascular disease. In the present review, we intend to shed light on the possible effects and molecular mechanism of natural agents like polyphenols via regulating mTOR.

Combination of exercise training and L-arginine reverses aging process through suppression of oxidative stress, inflammation, and apoptosis in the rat heart.

Aging-induced progressive decline of molecular and metabolic factors in the myocardium is suggested to be related with heart dysfunction and cardiovascular disease. Therefore, we evaluated the effects of exercise training and L-arginine supplementation on oxidative stress, inflammation, and apoptosis in ventricle of the aging rat heart. Twenty-four 24-month-aged Wistar rats were randomly divided into four groups: the aged control, aged exercise, aged L-arginine (orally administered with 150 mg/kg for 12 weeks), and aged exercise + L-arginine groups. Six 4-month-old rats were also considered the young control. Animals with training program performed exercise on a treadmill 5 days/week for 12 weeks. After 12 weeks, protein levels of Bax, Bcl-2, pro-caspase-3/cleaved caspase-3, cytochrome C, and heat shock protein (HSP)-70 were assessed. Tissue contents of total anti-oxidant capacity, superoxide dismutase, catalase, and levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, and IL-6 were analyzed. Histological and fibrotic changes were also evaluated. Treadmill exercise and L-arginine supplementation significantly alleviated aging-induced apoptosis with enhancing HSP-70 expression, increasing anti-oxidant enzyme activity, and suppressing inflammatory markers in the cardiac myocytes. Potent attenuation in apoptosis, inflammation, and oxidative stress was indicated in the rats with the combination of L-arginine supplementation and exercise program in comparison with each group (p < 0.05). In addition, fibrosis percentage and collagen accumulation were significantly lower in the rats with the combination treatment of L-arginine and exercise (p < 0.05). Treadmill exercise and L-arginine supplementation provided protection against age-induced increase in the myocyte loss and formation of fibrosis in the ventricle through potent suppression of oxidative stress, inflammations, and apoptosis pathways.

Toll-like receptors as novel therapeutic targets for herpes simplex virus infection.

Seropositivity for HSV reaches more than 70% within the world population, and yet no approved vaccine exists. While HSV1 is responsible for keratitis, encephalitis, and labialis, HSV2 carriers have a high susceptibility to other STD infections, such as HIV. Induction of antiviral innate immune responses upon infection depends on a family of pattern recognition receptors called Toll-like receptors (TLR). TLRs bridge innate and adaptive immunity by sensing virus infection and activating antiviral immune responses. HSV adopts smart tricks to evade innate immunity and can also manipulate TLR signaling to evade the immune system or even confer destructive effects in favor of virus replication. Here, we review mechanisms by which HSV can trick TLR signaling to impair innate immunity. Then, we analyze the role of HSV-mediated molecular cues, in particular, NF-κB signaling, in promoting protective versus destructive effects of TLRs. Finally, TLR-based therapeutic opportunities with the goal of preventing or treating HSV infection will be discussed.

Targeting STATs in neuroinflammation: The road less traveled!

JAK/STAT transduction pathway is a highly conserved pathway implicated in regulating cellular proliferation, differentiation, survival and apoptosis. Dysregulation of this pathway is involved in the onset of autoimmune, haematological, oncological, metabolic and neurological diseases. Over the last few years, the research of anti-neuroinflammatory agents has gained considerable attention. The ability to diminish the STAT-induced transcription of inflammatory genes is documented for both natural compounds (such as polyphenols) and chemical drugs. Among polyphenols, quercetin and curcumin directly inhibit STAT, while Berberis vulgaris L. and Sophora alopecuroides L extracts act indirectly. Also, the Food and Drug Administration has approved several JAK/STAT inhibitors (direct or indirect) for treating inflammatory diseases, indicating STAT can be considered as a therapeutic target for neuroinflammatory pathologies. Considering the encouraging data obtained so far, clinical trials are warranted to demonstrate the effectiveness and potential use in the clinical practice of STAT inhibitors to treat inflammation-associated neurodegenerative pathologies.

Effect of Root Extracts of Medicinal Herb Glycyrrhiza glabra on HSP90 Gene Expression and Apoptosis in the HT-29 Colon Cancer Cell Line.

Colorectal cancer is one of the most common lethal cancer types worldwide. In recent years, widespread and large-scale studies have been done on medicinal plants for anti-cancer effects, including Glycyrrhiza glabra. The aim of this study was to evaluate the effects of an ethanol extract Glycyrrhiza glabra on the expression of HSP90, growth and apoptosis in the HT-29 colon cancer cell line. HT-29 cells were treated with different concentrations of extract (50,100,150, and 200 µg/ml). For evaluation of cell proliferation and apoptosis, we used MTT assay and flow cytometry technique, respectively. RT-PCR was also carried out to evaluate the expression levels of HSP90 genes. Results showed that Glycyrrhiza glabra inhibited proliferation of the HT-29 cell line at a concentration of 200 µg/ml and this was confirmed by the highest rate of cell death as measured by trypan blue and MTT assays. RT-PCR results showed down-regulation of HSP90 gene expression which implied an ability of Glycyrrhiza glabra to induce apoptosis in HT-29 cells and confirmed its anticancer property. Further studies are required to evaluate effects of the extract on other genes and also it is necessary to make an extensive in vivo biological evaluation and subsequently proceed with clinical evaluations.